1. Field of the Invention
The present invention relates generally to a system and method for manufacturing oral osmotic drug delivery devices. In particular, the present invention is directed towards deriving a mathematical model of a relationship between parameters used in manufacturing the devices, using statistical analysis of historical data. The derived relationship may then be used to control the parameters so that the active drug substance within the product is delivered at a desired rate. The present invention also relates to methods of administering the oral osmotic drug delivery devices to subjects. The present invention further relates to methods of making particles of a drug and one or more excipients.
2. Description of Related Art
Unless conventional rapid acting drug therapy is carefully administered at frequent intervals to maintain an effective steady state level of the therapeutic agent or active substance, peaks and valleys in the level of the active drug in the patient's system can occur because of, for example, rapid absorption and systemic excretion of the compound and occurrence of metabolic inactivation, thereby producing special problems in maintenance therapy of the patient. This result can cause the active substance to be delivered to the patient's system in a dosage that may be too high and to regions of the body where the active substance may not be at its most effective.
These problems can be overcome to some extent by controlled release forms of the therapeutic agent or active substance. These forms are also referred to as controlled release sustained release, retarded release, and slow release.
Controlled release dosage ideally provides and maintains therapeutic concentrations of the active substance in the patient's system throughout the dosing interval with an acceptable peak/valley concentration ratio. Controlled release formulations are designed to provide a longer period of pharmacologic action after administration than is ordinarily obtained after administration of immediate-release dosage forms. Controlled release compositions may be used, for example, to maintain a desired concentration of said therapeutic agent in the patient's system for a longer duration than would occur if conventional rapid release dosage forms were to be administered. Such longer periods of response provide for therapeutic benefits that are not achieved with corresponding short acting, immediate release preparations. Thus, therapy may be continued without interrupting the sleep of a patient, for example, which can be of particular importance when treating a patient for moderate to severe pain, or for treating a debilitated patient for whom sleep is essential. A further general advantage of longer acting drug preparations is improved patient compliance resulting from the avoidance of missed doses through patient forgetfulness.
The benefits of controlling the release of the active ingredient to sustain a constant release over a predetermined amount of time include: improved delivery to the required site; improved delivery at the required rate by reducing swings of drug levels in the patient's system; allowing fewer doses per day; reduced dangers of overdosing; avoidance of side effects from rapid increases in drug concentration within a patient's system; prevention of drug concentration in the patient's system from dropping below therapeutic levels; and assurance of more efficient dosages. In order to accomplish these goals, the controlled release formulation must provide a reliable dissolution and release rate of the active substance.
In the past, the manufacturing process of controlled release tablets has not led to uniform release rates and dissolution of the active substance. Thus, the drug delivery rate can fall above or below the desired delivery rate. When the delivery rate for a controlled release tablet falls sufficiently outside the approved specifications, the tablet cannot be placed in the market to be used by a patient. Thus, it is necessary to have a manufacturing process that consistently produces tablets with a delivery rate of the active substance within the desired range and that is amenable to large scale manufacturing processes. It is also necessary to have a manufacturing process that allows for particles of the active substance and excipients to fall within specified, predetermined size limitations.